J. Carlsson et al., STRATEGY FOR BORON NEUTRON-CAPTURE THERAPY AGAINST TUMOR-CELLS WITH OVER-EXPRESSION OF THE EPIDERMAL GROWTH FACTOR-RECEPTOR, International journal of radiation oncology, biology, physics, 30(1), 1994, pp. 105-115
Citations number
99
Categorie Soggetti
Oncology,"Radiology,Nuclear Medicine & Medical Imaging
Purpose: Gliomas, squamous carcinomas and different adenocarcinomas fr
om breast, colon and prostate might have an increased number of epider
mal growth factor (EGF) receptors. The receptors are, in these cases,
candidates for binding of receptor specific toxic conjugates that migh
t inactivate cellular proliferation. The purpose of this study was to
evaluate whether it is reasonable to try ligand-dextran based conjugat
es for therapy. Methods and Materials: EGF or TGF alpha were conjugate
d to dextran and binding, internalization, retention and degradation o
f eight types of such conjugates were analyzed in EGF-receptor amplifi
ed glioma cells. The conjugates were labelled with radioactive nuclide
s to allow detection and two of the conjugates were carrying boron in
the form of carboranyl amino acids or aminoalkyl-carboranes. Comparati
ve binding tests, applying I-125-EGF, were made with cultured breast,
colon and prostate adenocarcinoma, glioma and squamous carcinoma cells
. Some introductory tests to label with Br-76 for positron emission to
mography and with I-131 for radionuclide therapy were also made. Resul
ts: The dextran part of the conjugates did not prevent receptor specif
ic binding. The amount of receptor specific binding varied between the
different types of conjugates and between the tested celltypes. The d
extran part improved intracellular retention and radioactive nuclides
were retained for at least 20-24 h. The therapeutical effect improved
when I-131 was attached to EGF-dextran instead of native EGF. Conclusi
on: The improved cellular retention of the ligand-dextran conjugates i
s an important property since it gives extended exposure time when rad
ionuclides are applied and flexibility in the choice of time for appli
cation of neutrons in boron neutron capture therapy (BNCT). It is poss
ible that ligand-dextran mediated BNCT might allow, if the applied neu
tron fields covers rather wide areas around the primary tumor, locally
spread cells that otherwise would escape treatment to be inactivated.